EP-A-EP1943520 and WO2007045996 describe an in vitro method for the prognosis of patients for progression of a cancer and/or of the survival, and/or the prediction of response to treatment (chemotherapy, radiotherapy, biotherapy, immunotherapy) which method comprises the following steps:
a) quantifying, in a tumour tissue sample from said patient, at least one biological marker indicative of the status of the local adaptive immune reaction of said patient; and
b) comparing the value obtained at step a) for said at least one biological marker with a predetermined reference value for the same biological marker; which predetermined reference value is correlated with a specific prognosis of progression of said cancer or survival of said patient or prediction of treatment response (such as chemotherapy, radiotherapy, biotherapy, immunotherapy) to anticipate the “good responder” vs “bad responder”.
The tumour tissue sample may be selected from the group consisting in (i) a global primary tumour (as a whole), (ii) a tissue sample from the tumour, (iii) a tissue sample from the tissue directly surrounding the tumour which tissue may be more specifically named the “invasive margin” of the tumour, (iv) lymphoid islets in close proximity with the tumour, (v) the lymph nodes located at the closest proximity of the tumour, (vi) a tumour biopsy performed prior surgery, and (vii) a distant metastasis.
The biological marker is preferably quantified, at step a), in tumour samples collected from two regions of the tumour, respectively (i) the tumour (CT) and (ii) the invasive margin of the tumour (IM).
The above method was implemented on tissue microarrays (TMAs). However, most of the steps of the process are implemented manually and problems with reproducibility of measurements might be observed. For example differences between pathologists for the selection of tumour areas to punch can occur, based on the Haematoxylin-Eosin counterstaining examination. In addition, a difficulty to punch exactly the area selected by the pathologist is observed. Such typical errors can occur at each step. Although the method described in these documents makes it possible to obtain high-performance for predicting the survival of patients with cancer, research is still going on into methods with even better qualities, particularly as regards automation reproducibility and comparability of the results.
As highlighted by Halama et al in Quantification of prognostic immune cell markers in colorectal cancer using whole slide imagining tumour maps, analytical and quantitative cytology and histology, Vol. 32, 6, December 2010, pp. 333-340, sampling histologic probes using tissue micro-arrays (TMAs) is especially problematic in the case of a spatial heterogeneity of the target molecule as it is frequently observed in cancer tissue. Halama et al proposes full tissue slide microscopy for data acquisition. However the study does not demonstrate a specific diagnostic algorithm producing a parameter able to interpret the spatial heterogeneity of the tumour. He concludes that until this diagnostic algorithm is created and a follow-up study is performed he cannot know if the tumour map will have prognostic value in a single patient.